The present invention relates to pharmaceutical formulations in the form of agglomerates for the production of rapidly disintegrating tablets, comprising sugar or sugar alcohols, disintegrant and water-insoluble polymers.
Tablets which disintegrate rapidly in the mouth and/or dissolve rapidly are becoming increasingly important for the oral administration of medicinal substances. Such tablets must disintegrate within a short time, preferably within 30 seconds, in the oral cavity and have a pleasant taste and must not leave behind a gritty sensation. Furthermore they should be easy to produce, with direct tableting having considerable advantages over wet granulation, and should have high mechanical strength so that they withstand packaging procedures, transport and also pressing out from packaging without damage.
The products and processes described to date do not meet these requirements or do so only very inadequately.
Rapidly disintegrating tablets frequently consist of sugar and sugar alcohols, effervescent systems, microcrystalline cellulose and other water-insoluble fillers, calcium hydrogen phosphate, cellulose derivatives, cornstarch or polypeptides. Furthermore, water-soluble polymers, conventional disintegrants (crosslinked PVP, sodium and calcium salts of crosslinked carboxymethylcellulose, the sodium salt of carboxymethyl starch, low-substituted hydroxypropylcellulose L-HPC) and substantially inorganic water-insoluble constituents (silicas, silicates, inorganic pigments) are used. Furthermore, the tablets may also comprise surfactants.
WO 2003/051338 describes a directly tablettable and readily compressible excipient formulation which comprises mannitol and sorbitol. First, art excipient premix is prepared by dissolution of mannitol and sorbitol in water and subsequent spray drying (customary spray drying and SBD method). Mannitol may also be added to this coprocessed mixture. Tablets which additionally comprise disintegrant, glidant, pigment and an active ingredient are said to disintegrate within 60 seconds in the oral cavity.
US 2002/0071864 A1 describes a tablet which disintegrates within 60 seconds in the oral cavity and is mainly formulated from a physical mixture of spray-dried mannitol and a coarse-particle crosslinked polyvinylpyrrolidone and a limited selection of active ingredients. These tablets have a hardness of about 40 N and produce an unpleasant, gritty mouthfeel.
According to U.S. Pat. No. 6,696,085 B2 a methacrylic acid copolymer of type C is to be used as a disintegrant. The methacrylic acid copolymer of type C is a polymer which is resistant to gastric fluid and insoluble in the acidic pH range but water-soluble in the pH range of 7 as is present in the oral cavity. In addition to low hardness (<20 N), the tablets have high friability (>7%) and have a high proportion in the region of 15% by weight of a coarse-particle disintegrant. They consequently have low mechanical strength and, owing to the high proportion of coarse-particle disintegrant, produce an unpleasant, gritty mouthfeel.
EP 0839526 A2 describes a pharmaceutical dosage form consisting of an active ingredient, erythritol, crystalline cellulose and a disintegrant. Furthermore, mannitol is incorporated and crosslinked polyvinylpyrrolidone is used as a disintegrant, so that a physical mixture forms. The tablets are said to decompose within 60 seconds in the oral cavity.
The application JP 2004-265216 describes a tablet which disintegrates in the mouth within 60 seconds and consists of an active ingredient, a water-soluble polyvinyl alcohol/polyethylene glycol copolymer, sugar/sugar alcohol (mannitol) and disintegrant.